chr5-114362882-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_021614.4(KCNN2):c.743C>T(p.Pro248Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,598,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P248H) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
KCNN2
NM_021614.4 missense
NM_021614.4 missense
Scores
3
7
4
Clinical Significance
Conservation
PhyloP100: 4.23
Genes affected
KCNN2 (HGNC:6291): (potassium calcium-activated channel subfamily N member 2) Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNN2 | NM_021614.4 | c.743C>T | p.Pro248Leu | missense_variant | 1/8 | ENST00000673685.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNN2 | ENST00000673685.1 | c.743C>T | p.Pro248Leu | missense_variant | 1/8 | NM_021614.4 | P2 | ||
KCNN2 | ENST00000512097.10 | c.941C>T | p.Pro314Leu | missense_variant | 6/13 | 5 | A2 | ||
KCNN2 | ENST00000631899.2 | c.146C>T | p.Pro49Leu | missense_variant | 1/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000879 AC: 2AN: 227568Hom.: 0 AF XY: 0.00000795 AC XY: 1AN XY: 125720
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GnomAD4 exome AF: 0.0000111 AC: 16AN: 1446306Hom.: 0 Cov.: 77 AF XY: 0.00000834 AC XY: 6AN XY: 719834
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74306
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | KCNN2: PP3 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
REVEL
Uncertain
Polyphen
0.0010
.;B
Vest4
0.51
MutPred
0.18
.;Gain of sheet (P = 0.0166);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at